ASSESSMENT OF ATRIAL-NATRIURETIC-PEPTIDE RESISTANCE IN CIRRHOSIS WITHHEAD-OUT WATER IMMERSION AND ATRIAL-NATRIURETIC-PEPTIDE INFUSION

The nature of sodium retention in cirrhosis complicated by ascites has been studied for the last 30 years. Resistance to the natriuretic act ion of atrial natriuretic peptide (ANP) may play a potential role in t his sodium retention. To further evaluate this possibility, we studied 12 patients with biopsy-proven cirrhosis and ascites on 2 consecutive days after a 7-day period off diuretics while receiving a 20 mmol/day sodium restricted diet. Following a crossover design, patients underw ent head-out water immersion (HWI) for 3 h and were infused with a ce- human ANP for 2 h on 2 consecutive days. Blood and urine samples were collected hourly. Five patients displayed a natriuretic response to HW I, sufficient to achieve negative sodium balance, and these patients w ere termed responders. Each of these five patients also displayed a na triuretic response to ANP infusion. In contrast, the other seven patie nts (nonresponders) consistently failed to develop a natriuretic respo nse to either maneuver. The two groups had similar elevations in plasm a ANP concentrations, but at baseline differed in terms of plasma sodi um, plasma renin activity, and serum aldosterone. Despite higher serum aldosterone concentrations, nonresponders excreted less potassium tha n responders during the peak effect of the interventions, suggesting g reater sodium delivery to the aldosterone-sensitive nephron segment in responders. We conclude that the inability to mount an adequate sodiu m excretory response to HWI in patients with cirrhosis may be conveyed through increased antinatriuretic factors that decrease the sodium de livery to the medullary collecting duct and inhibit the natriuretic ef fect of ANP at that site.